Cytokines are proteins secreted by a cell of the immune system and transduce a signal to a specific cell. Cytokines have various kinds, and many of them are especially associated with immunity and inflammation and also associated with cell proliferation, cell differentiation, cell death, wound healing and the like (Curr Opin Cell Biol. 1991 April; 3(2):171-5.).
The Janus kinase (JAK) family plays a role in cytokine-dependent regulation of the function of cells associated with growth and immune response. JAK family consists of four kinds of Janus kinases (JAK1 (Janus kinase 1), JAK2 (Janus kinase 2), JAK3 (Janus kinase 3) and TYK2 (tyrosine kinase 2)). Among them, JAK1 is known to be involved in signal transduction of cytokines such as IL(interleukin)-2, IL-4, IL-7, IL-15, IL-21, IL-6, OSM (oncostatin M), IL-10 family, IFN(interferon)-α, IFN-β, IFN-γ and the like (Nature Immunology 10, 356-360 (2009)). TYK2 is known to be involved in signal transduction of cytokines such as IFN-α, IFN-β, IL-6, IL-10 family (IL-10, IL-19, IL-20, IL-22, IL-28, IL-29), IL-12, IL-23 and the like (Nature Immunology 10, 356-360 (2009), New York Academy of Science 1246, 34-40 (2011)). In addition, these cytokines play an important role in immune response when exist in an appropriate amount. However, excessive production of them is involved in many autoimmune diseases such as rheumatoid arthritis, psoriasis, inflammatory bowel disease, Sjogren's syndrome, Behcet's syndrome, multiple sclerosis, systemic lupus erythematosus and the like (Journal of Allergy and Clinical Immunology 127, 3, 701-721.e70 (2011), Cytokine & Growth Factor Reviews 19, 41-52 (2008), Invest Ophthalmol Vis Sci. 2008 July; 49(7):3058-3064, Ann Rheum Dis. 2010 July; 69(7):1325-1328).
Tocilizumab, which is an anti-IL-6 receptor monoclonal antibody, has been approved as a therapeutic drug for rheumatoid arthritis in Japan, Europe and the United States, and furthermore, clinical trials for various diseases in which the IL-6 signaling pathway is suggested to be involved are performed. From the foregoing, a JAK1 inhibitor can be a therapeutic drug for various autoimmune diseases such as rheumatoid arthritis, psoriasis, inflammatory bowel disease, Sjogren's syndrome, Behcet's syndrome, multiple sclerosis, systemic lupus erythematosus and the like (Clinical Science 122, 143-159 (2012)).
Moreover, JAK signal is also associated with differentiation and growth of various carcinoma cells (Trends Biochem. Sci. 33, 122-131 (2008)). Particularly, JAK1 is associated with leukemia and uterine leiomyosarcoma due to the constant activation therein (J Exp Med 205, 751-758 (2008), Oncogene 25, 4016-4026, (2006)). In addition, clinical trials of antibody and low molecule compound which target at IL-6 are performed for cancer diseases such as prostate cancer, multiple myeloma, cachexia, myelofibrosis and the like (Clinical Science 122, 143-159 (2012), The New England Journal of Medicine 363, 1117-1127 (2010)). From the foregoing, a JAK1 inhibitor can be a therapeutic drug for cancer diseases such as leukemia, uterine leiomyosarcoma, prostate cancer, multiple myeloma, cachexia, myelofibrosis and the like.
Ustekinumab, which is an anti-IL-12/23 monoclonal antibody, has been approved as a therapeutic drug for moderate to severe psoriasis patient in Europe, and furthermore, clinical trials for various diseases in which the IL-12/23 signaling pathway is suggested to be involved are performed (J Immunol. 2010 May 1; 184 (9): 4605-9). In addition, involvement of IL-23 signal pathway in the central nervous system diseases such as Alzheimer's disease (e.g., dementia of Alzheimer type and the like) and the like has also been suggested (Nat Med. 2012 December; 18(12):1812-9). In view of the above, a TYK2 inhibitor can be a therapeutic drug for various autoimmune diseases such as rheumatoid arthritis, psoriasis, inflammatory bowel disease, Sjogren's syndrome, Behcet's syndrome, multiple sclerosis, systemic lupus erythematosus and the like, or a therapeutic drug for central nervous system diseases such as Alzheimer's disease (e.g., dementia of Alzheimer type and the like) and the like (Front Biosci. 2011 Jun. 1; 17:3214-32).
Examples of the compound having a structure similar to the compound described in the present specification include the following compounds.    (1) A compound represented by the following formula:
(non-patent document 1).    (2) A compound represented by the following formula:
(non-patent document 2).    (3) A compound represented by the following formula:
(non-patent document 3).    (4) A compound represented by the following formula:
(non-patent document 4).    (5) The following compounds are registered in Chemical Abstract.    1) Registry Number: 1018564-99-2
    2) Registry Number: 1018564-95-8
    3) Registry Number: 1018564-87-8
    4) Registry Number: 1018497-28-3
    5) Registry Number: 1018497-20-5
    6) Registry Number: 1018497-18-1
    7) Registry Number: 1018497-16-9
    8) Registry Number: 1018497-14-7
    9) Registry Number: 1018497-12-5
    10) Registry Number: 1018497-10-3
    11) Registry Number: 1018274-50-4
    12) Registry Number: 1018249-54-1
    13) Registry Number: 1018249-46-1
    14) Registry Number: 1018497-28-3
    15) Registry Number: 908069-44-3
    16) Registry Number: 908068-91-7
    17) Registry Number: 908069-29-4
    18) Registry Number: 907970-80-3
